Stimulation of the delta (1)-opioid receptor confers cardioprotection to th
e ischemic myocardium. We examined the role of protein kinase C (PKC) after
delta -opioid receptor stimulation with TAN-67 or D-Ala(2)-D-Leu(5)-enkeph
alin (DADLE) in a rat model of myocardial infarction induced by a 30-min co
ronary artery occlusion and 2-h reperfusion. Infarct size (IS) was determin
ed by tetrazolium staining and expressed as a percentage of the area at ris
k (IS/AAR). Control animals, subjected to ischemia and reperfusion, had an
IS/AAR of 59.9 +/- 1.8. DADLE and TAN-67 administered before ischemia signi
ficantly reduced IS/AAR (36.9 +/- 3.9 and 36.7 +/- 4.7, respectively). The
delta (1)-selective opioid antagonist 7-benzylidenenaltrexone (BNTX) abolis
hed TAN-67-induced cardioprotection (54.4 +/- 1.3). Treatment with the PKC
antagonist chelerythrine completely abolished DADLE- (61.8 +/- 3.2) and TAN
-67-induced cardioprotection (55.4 +/- 4.0). Similarly, the PKC antagonist
GF 109203X completely abolished TAN-67-induced cardioprotection (54.6 +/- 6
.6). Immunofluorescent staining with antibodies directed against specific P
KC isoforms was performed in myocardial biopsies obtained after 15 min of t
reatment with saline, chelerythrine, BNTX, or TAN-67 and chelerythrine or B
NTX in the presence of TAN-67. TAN-67 induced the translocation of PKC-alph
a to the sarcolemma, PKC-beta (1) to the nucleus, PKC-delta to the mitochon
dria, and PKC-epsilon to the intercalated disk and mitochondria. PKC transl
ocation was abolished by chelerythrine and BNTX in TAN-67-treated rats. To
more closely examine the role of these isoforms in cardioprotection, we uti
lized the PKC-delta selective antagonist rottlerin. Rottlerin abolished opi
oid-induced cardioprotection (48.9 +/- 4.8) and PKC-delta translocation wit
hout affecting the translocation of PKC-alpha,- beta (1), or -epsilon. Thes
e results suggest that PKC-delta is a key second messenger in the cardiopro
tective effects of delta (1)-opioid receptor stimulation in rats.